The Malaria Genomic Unit uses the malaria parasite genome databases and develops new resources to study the mechanism of drug resistance, gene regulation during parasite sexual development, and parasite population diversity and evolution. Now we have finished collecting single nucleotide polymorphisms (SNPs) from 3539 genes on all of the 14 chromosomes of Plasmodium falciparum. We are developing a platform that will allow us to genotype large number of SNPs. All the SNP information and some DNA have been sent a company; and we are in the process of evaluating a SNP typing chip. A manuscript describing this multi-year project is being submitted.? ? We have finished the project studying chromosomal haplotypes, population structures, and recombination rate variation and have published a paper in PLoS Biology.? ? The project studying the origin of P. vivax parasite has been completed too. We sequenced the mitochondrial genome from 176 P. vivax isolates and 5 other primate malaria species. Our data support the hypothesis of host switches and origin of P. vivax from Asian monkeys. The results were published in Mol. Biol. Evol.? ? Another major effort of our laboratory is to study gene expression and regulation associated with the parasite sexual differentiation. We have identified a gene that may play a key role in gametocyte development using microarray and genetic mapping. The results from this study have also been published in PNAS.? ? We are in the process of growing parasite isolates for genotyping using the SNP typing technology we are developing and a high density Affymatrix tiling array. We hope to use these methods and field parasites to locate loci that are associated with different drug resistant and parasite development phenotypes.? ? We are still interested in various aspects of parasite sexual development, particularly the biological functions of Pfmdv1 and other genes that may involve in the process of gametocyte development.?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000892-06
Application #
7303881
Study Section
(LPD)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2006
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Raj, Dipak Kumar; Mu, Jianbing; Jiang, Hongying et al. (2009) Disruption of a Plasmodium falciparum multidrug resistance-associated protein (PfMRP) alters its fitness and transport of antimalarial drugs and glutathione. J Biol Chem 284:7687-96
Li, Jian; Zhang, Yanhui; Sullivan, Margery et al. (2007) Typing Plasmodium yoelii microsatellites using a simple and affordable fluorescent labeling method. Mol Biochem Parasitol 155:94-102
Mu, Jianbing; Awadalla, Philip; Duan, Junhui et al. (2007) Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome. Nat Genet 39:126-30
Su, Xinzhuan; Hayton, Karen; Wellems, Thomas E (2007) Genetic linkage and association analyses for trait mapping in Plasmodium falciparum. Nat Rev Genet 8:497-506
Lu, Fangli; Jiang, Hongying; Ding, Jinhui et al. (2007) cDNA sequences reveal considerable gene prediction inaccuracy in the Plasmodium falciparum genome. BMC Genomics 8:255
Bockhorst, Joseph; Lu, Fangli; Janes, Joel H et al. (2007) Structural polymorphism and diversifying selection on the pregnancy malaria vaccine candidate VAR2CSA. Mol Biochem Parasitol 155:103-12
Cui, Long; Miao, Jun; Furuya, Tetsuya et al. (2007) PfGCN5-mediated histone H3 acetylation plays a key role in gene expression in Plasmodium falciparum. Eukaryot Cell 6:1219-27
Gaur, Deepak; Furuya, Tetsuya; Mu, Jianbing et al. (2006) Upregulation of expression of the reticulocyte homology gene 4 in the Plasmodium falciparum clone Dd2 is associated with a switch in the erythrocyte invasion pathway. Mol Biochem Parasitol 145:205-15
Jiang, H; Joy, D A; Furuya, T et al. (2006) Current understanding of the molecular basis of chloroquine-resistance in Plasmodium falciparum. J Postgrad Med 52:271-6
Chiang, Peter K; Bujnicki, Janusz M; Su, Xinzhuan et al. (2006) Malaria: therapy, genes and vaccines. Curr Mol Med 6:309-26

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